Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms.

Mahru C An, Weichun Lin, Jiefei Yang, Bertha Dominguez, Daniel Padgett, Yoshie Sugiura, Prafulla Aryal, Thomas W Gould, Ronald W Oppenheim, Mark E Hester, Brian K Kaspar, Chien-Ping Ko, Kuo-Fen Lee

Proceedings of the National Academy of Sciences of the United States of America 2010 Jun 8

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Emerging evidence suggests that the neurotransmitter acetylcholine (ACh) negatively regulates the development of the neuromuscular junction, but it is not clear if ACh exerts its effects exclusively through muscle ACh receptors (AChRs). Here, we used genetic methods to remove AChRs selectively from muscle. Similar to the effects of blocking ACh biosynthesis, eliminating postsynaptic AChRs increased motor axon branching and expanded innervation territory, suggesting that ACh negatively regulates synaptic growth through postsynaptic AChRs. However, in contrast to the effects of blocking ACh biosynthesis, eliminating postsynaptic AChRs in agrin-deficient mice failed to restore deficits in pre- and postsynaptic differentiation, suggesting that ACh negatively regulates synaptic differentiation through nonpostsynaptic receptors. Consistent with this idea, the ACh agonist carbachol inhibited presynaptic specialization of motorneurons in vitro. Together, these data suggest that ACh negatively regulates axon grow th and presynaptic specialization at the neuromuscular junction through distinct cellular mechanisms.

Citation

Mahru C An, Weichun Lin, Jiefei Yang, Bertha Dominguez, Daniel Padgett, Yoshie Sugiura, Prafulla Aryal, Thomas W Gould, Ronald W Oppenheim, Mark E Hester, Brian K Kaspar, Chien-Ping Ko, Kuo-Fen Lee. Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms. Proceedings of the National Academy of Sciences of the United States of America. 2010 Jun 8;107(23):10702-7